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Dietary uridine supplementation decreases tumor number in Apc(Min/+) mice (829.11)
Author(s) -
Field Martha,
Stover Patrick
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.829.11
Subject(s) - thymidylate synthase , nucleotide salvage , thymidine kinase , deoxyuridine , thymidine , uridine , colorectal cancer , methionine , dna synthesis , biology , methyltransferase , biochemistry , cancer , cancer research , methylation , microbiology and biotechnology , nucleotide , genetics , dna , gene , rna , fluorouracil , virus , herpes simplex virus , amino acid
Colorectal cancer affects 1.23 million people and accounts for more than 600,000 deaths each year worldwide. Deficiency of methyl donors including folate and methionine has been linked to increased colon cancer risk in experimental and epidemiological studies. The Apc(Min/+) mouse model is a powerful tool for studying the genetic and dietary mechanisms which contribute to intestinal cancer phenotypes. A previous study showed that Apc(Min/+) mice also lacking one copy of the Shmt1 gene, which results in perturbed de novo thymidylate (dTMP) synthesis, displayed increased intestinal tumor number that was exacerbated by folate deficiency. dTMP is the only nucleotide that is synthesized at the replication fork as needed for DNA replication and repair. dTMP can either be synthesized de novo from the folate‐dependent reductive methylation of deoxyuridylate (dUMP) to dTMP through a multi‐enzyme complex or can be generated by phosphorylating thymidine to dTMP by the salvage pathway enzyme thymidine kinase (TK1). In this study, we sought to determine whether dietary supplementation of dTMP precursors (thymidine, deoxyuridine or uridine) could modify tumor number in the Apc(Min/+) model. Surprisingly, dietary uridine supplementation reduced intestinal tumor number and tumor burden by 40% (p<0.05) relative to the control diet; neither thymidine nor deoxyuridine affected tumor number. Grant Funding Source : Supported by NIH R37DK58144